Protein-based therapeutics have proven highly effective for a variety of disorders, injuries and diseases. Apart from the performance challenges associated with protein-based therapeutics, numerous other types of challenges arise during the development of such therapeutics, including protein processing considerations such as ease and cost of manufacturing, stability and shelf-life, as well as modes of administration, dosages and form of effective dosage, to name but a few.
Certain therapeutically significant proteins are particularly difficult because of their inherent insolubility under physiological conditions, such as but not limited to physiological pH. This insolubility is exacerbated when highly concentrated aqueous solutions are desirable. One class of proteins which is inherently insoluble under physiological conditions is the TGF-beta superfamily of cysteine knot proteins. A similarly behaving subfamily includes the Bone Morphogenetic Proteins (BMPs), for example, BMP-2, BMP-7 (also known as OP-1), GDF-5 (also known as CDMP-1 and MP-52), GDF-6 (also known as BMP-13 and CDMP-2).
It is an object of the present invention to provide highly concentrated aqueous protein preparations of such proteins, including but not limited to, BMPs. It is a further object to provide methods of treatment of skeletal and non-skeletal disorders, injuries and diseases using such preparations.